A model suitable for investigating the action of aflatoxin, a potent hepatic carcinogen, has been developed in our laboratory. Chronic aspergillosis is imposed in rats by injecting mycelia, spores or presumed yeast forms of Aspergillus parasiticus. With this model we plan to investigate if neoplastic changes can be produced during the in vivo production of aflatoxin and other mycotoxins, which A. parasiticus produces. The occurrence of neoplastic and other pathological changes in animals chronically infected with A. parasiticus will be examined by histopathological immunobiological and biochemical techniques. This study will include the determination of both the humoral and cellular responses to aflatoxin, 3-nitropropionic acid and kojic acid. Sites of action of these mycotoxins will be investigated using immunohistochemical procedures. Possible mechanisms of the pathological action of aflatoxins will be investigated by studying hormone-aflatoxin interactions at the cytoplasmic and nuclear receptor sites. In addition, an attempt will be made to demonstrate the formation of a highly reactive electrophilic residue of aflatoxin, a form wich might be the active carcinogen. The toxigenic and pathogenic properties of the spores, mycelia and yeast forms of A. parasiticus will be compared.